5Peptides derived from CgB, being more extensively processed than CgA in
most systems and species (Strub et al. 1995 ), may have specific regulatory func-
tions yet to be unravelled. SgII, on the other hand, serves a prohormone for only
one conspicuously active principle, secretoneurin (Kirchmair et al. 1993 , Trudeau
et al. 2012 ), nevertheless engaged in a wide range of modulating activities related
to tissue repair (Helle 2010a). Stimulated polymorphonuclear neutrophils, when
accumulated in response to invading microorganism, tissue inflammation and at
sites of mechanical injury, represent a non-neuroendocrine source of CgA pep-
tides that may affect a wide range of cells involved in inflammatory responses
(Lugardon et al. 2000 ; Zhang et al. 2009 ). Among them we find the vascular endo-
thelium, the endocardium and the epithelial cells, other leucocytes, fibroblasts,
cardiomyocytes, vascular and intestinal smooth muscle cells (Helle et al. 2007 ;
Helle 2010a, b). Taken together, the release of CgA-derived peptides from gland
cells, nerve terminals and immunocytes would contribute to autocrine or para-
crine modulations locally while endocrine effects would result from their subse-
quent overflow to the circulation.
1.4.1 The Antimicrobial Peptides and Innate Immunity
Antimicrobial activities of peptides derived from the matrix of secretory granules in
the bovine adrenal medulla were first reported by Metz-Boutigue and colleagues in
1998. The first three peptides found to inhibit bacteria and fungal growth were
derived from the N-terminal domain of CgA (VS-I), the C-terminal end of CgB
(secretolytin) and the biphosphorylated C-terminal peptide of proenkephalin-A
(enkelytin). These peptides are active in a diverse range of organisms, including
prokaryotes, bivalves, frogs and mammals, suggesting an important role in innate
immunity, a mechanism shared by all vertebrates and present at birth as an evolu-
tionary ancient defence mechanism (Hoffmann et al. 1999 ; Metz-Boutigue et al.
2000 ). Another CgA peptide, catestatin, derived from CgA in keratinocytes, also
possess antimicrobial activity against gram-positive and gram-negative bacteria,
yeast and fungi, is active notably against skin pathogens and increases in skin in
response to injury and infection (Radek et al. 2008 ). So far, no antimicrobial activity
has been assigned to SN.
The innate immunity, independent of the adaptive immune responses, is used
by vertebrates as a means for short term protection against pathogenic microor-
ganisms. The need for new antimicrobial agents is now rapidly rising due to the
fast growing number of antibiotica-resistant bacteria. Accordingly, the interest in
antibacterial granin-derived peptides has grown exponentially. Their therapeutic
potentials are now under intensive elucidation in immunodeficient patients, in
chemotherapy, in organ grafting, and against antibiotica-resistant bacterial infec-
tions (Shooshtarizodeh et al. 2010 ).
History and Perspectives